What is the value of temporal artery biopsy in the diagnosis of GCA?

Giant cell arteritis (GCA) is a nasty inflammatory disorder that affects the large arteries. Because it characteristically involves the temporal artery, this form of vasculitis is also referred to as temporal arteritis. It usually affects people over the age of 50 years and manifests with sudden onset headache, scalp pain, and a thick, tender temporal artery. GCA is often accompanied by polymyalgia rheumatica (PMR) , a painful condition of the joints and muscles. The active systemic inflammation in GCA is often detected by the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) tests. These distinguishing features constitute most of the diagnostic criteria for GCA.

By National Institute of Standards and Technology – https://www.flickr.com/photos/usnistgov/5828207621/, Public Domain, Link

Most people with GCA however do not have all the ‘classical’ features of the disease. A high index of suspicion is therefore required to sniff out the duplicitous miscreant. It is particularly imperative to make the diagnosis as early as possible to prevent the dreaded complications of GCA, sudden blindness and stroke. The treatment of GCA, implemented according to established treatment guidelines, involves several months of oral steroids, drugs which cause immune suppression and a host of other side effects. It is therefore essential that the diagnosis of GCA is made correctly to avoid putting the patient on a long, risky, and unnecessary treatment.

By Henry Vandyke CarterHenry Gray (1918) Anatomy of the Human Body (See “Book” section below)Bartleby.com: Gray’s Anatomy, Plate 508, Public Domain, Link

The conventional method of establishing the definitive diagnosis of GCA is by performing a temporal artery biopsy. This involves taking a short segment of the temporal artery as it traverses the temple. This procedure however only confirms the diagnosis of GCA in 1335% of people with the condition. One reason the biopsy has such a poor sensitivity is that it is often performed after treatment has already commenced. Another reason the biopsy is often normal is that the inflammation in GCA occurs in patches, sparing large segments of the artery. Don’t even think about it-taking a longer biopsy segment does not increase the yield of temporal artery biopsy. Put another way, “specimen length is not associated with diagnostic yield of temporal artery biopsy.

By NephronOwn work, CC BY-SA 3.0, Link
What then is the value of the temporal artery biopsy in the diagnosis of GCA? This is the question posed by Bowling et al in their incisive paper titled Temporal artery biopsy in the diagnosis of giant cell arteritis: does the end justify the means? They reviewed 129 temporal artery biopsies and found that the clinical diagnosis of GCA was confirmed in only 13% of cases. Furthermore, the outcome of the biopsy rarely ever influenced the treatment; 87% of those with a normal biopsy result still continued their treatment. The miffed authors therefore rhetorically, and indignantly, asked: “can we justify invasive surgery to all patients on histological grounds when the results may not alter management?” 
Ipswich, Waterfront, Ipswich Campus, The Big Question Mark Sculpture. Martin Pettitt on Flikr. https://www.flickr.com/photos/mdpettitt/8671901426

This is an entirely reasonable question especially because there are other more accurate and less invasive ways of establishing the diagnosis of GCA. These include:

But the answer to the authors’ rhetorical question is anyones guess. It is a sad tradition of medicine that studies such as these take ages to change practice. Indeed I predict the the temporal artery biopsy will sidestep this minor hurdle and simply continue its long and agonising reign. Despair!
By No machine-readable author provided. Spekta assumed (based on copyright claims). – No machine-readable source provided. Own work assumed (based on copyright claims)., Public Domain, Link
You can at least read more on GCA in my previous blog post titled Advances in the management of giant cell arteritis. You may also explore these comprehensive neurochecklistsGiant cell arteritis (GCA): clinical featuresand Giant cell arteritis (GCA): diagnosis and management.

 

FDG. TRIUMF Lab on Flikr. https://www.flickr.com/photos/triumflab/8232448893

 

Advances in the management of giant cell arteritis

Giant cell arteritis (GCA), or temporal arteritis, is an affliction of older people. It results in headache and, more worryingly, blindness and stroke.

By Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 508, Public Domain, https://commons.wikimedia.org/w/index.php?curid=541352
By Henry Vandyke CarterHenry Gray (1918) Anatomy of the Human Body (See “Book” section below)Bartleby.com: Gray’s Anatomy, Plate 508, Public Domain, https://commons.wikimedia.org/w/index.php?curid=541352

 

The diagnosis of GCA is a clinical one. GCA diagnostic criteria stipulate, amongst other things, onset over the age of 50 years, and inflammation in the blood. A temporal artery biopsy may help to firm up the diagnosis. This is however not always readily available, and often falsely negative. Treatment with steroids is imperative to prevent sudden and irreversible visual loss.

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=37300811
By NephronOwn work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=37300811

 

Not much has changed in the world of giant cell arteritis since I was in medical school. Or so I thought. I couldn’t be more wrong. Here are 3 advances challenging the old order in the management of GCA.

 

1. Antiviral treatment

Varicella zoster virus. NIAID on Flikr. https://www.flickr.com/photos/niaid/5614251360
Varicella zoster virus. NIAID on Flikr. https://www.flickr.com/photos/niaid/5614251360

The cause of GCA is a mystery. One suspect is varicella zoster virus (VZV), of shingles fame. As shingles is also a disease of older people, it is no surprise that some researchers suspected a link between VZV and GCA. Writing in the Journal of Infectious Diseases in a paper titled Varicella Zoster Virus in Temporal Arteries of Patients With Giant Cell Arteritis, the authors detected VZV in the arteries of people with GCA, but did not pick up even a scent of VZV in control subjects who did not have GCA.

Another paper which strengthened the bond between GCA and VZV is in JAMA Neurology titled Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis. The authors of this study found VZV in the temporal arteries of 119 subjects with GCA. On the strength of this finding, the authors suggest GCA should be treated with anti-viral drugs. I am picking up the scent of a guideline on the way.

2. Monoclonal antibodies

B0007277 Monoclonal antibodies Wellcome Images on Flikr. https://www.flickr.com/photos/wellcomeimages/5814713820
B0007277 Monoclonal antibodies
Wellcome Images on Flikr. https://www.flickr.com/photos/wellcomeimages/5814713820

 

Some researchers, obviously uncomfortable with antiviral drugs, have looked elsewhere for ways to improve the treatment of GCA. And they found a champion in the monoclonal antibody Toclizumab. They published their findings in the Lancet under the title Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. The authors showed that adding Toclizumab to steroids in people with GCA led to sustained remission in 85% of cases; only 40% of the people on placebo achieved remission. I didn’t smell a rat here; the evidence seems quite convincing.

3. PET scan imaging

By Hg6996 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18889860
By Hg6996Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18889860

 

Temporal artery biopsy is hit and miss because GCA is a patchy process. Furthermore, biopsy is invasive and despised by doctor and patient equally. Ever keen to make things painless, doctors have looked at imaging of the artery as a substitute to biopsy. The imaging modalities on the cards include duplex ultrasound and magnetic resonance imaging (MRI). The prize must, however, go to positron emission tomography (PET) which has great potential as indicated in this review of PET scan in GCA. This suggests that PET scan aids the diagnosis, grading, and follow-up of GCA. Additionally, PET scan also identifies inflammation in other blood vessels. I perceive the end of the days of temporal artery biopsy!